Characterization of Sexual Dimorphism in the Brain

大脑性别二态性的表征

• 批准号: 10166218
• 负责人: Nirao Mahesh Shah
• 金额: $ 9.01万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10166218
• 关键词: Androgens; Animals; Aromatase; Brain; Brain region; Cells; Diagnostic; Disease; Enzymes; Estrogens; Female; Fiber; Functional disorder; Future; Goals; Health; Heart; Hypothalamic structure; Label; Light; Link; Medial; Mental disorders; Microscopic; Molecular; Nerve Degeneration; Neurologic; Neuronal Dysfunction; Neurons; Partner in relationship; Pathway interactions; Photometry; Physiological; Physiology; Regulation; Reproductive Behavior; Research; Rewards; Rodent; Social Interaction; Stress; Structure of terminal stria nuclei of preoptic region; Testing; Testosterone; Therapeutic; Work; brain behavior; insight; mature animal; neural circuit; parent project; response; sex; sexual dimorphism; stressor

Project Summary Social interactions are powerfully modulated by internal physiological state and future goals. The goal of our project is a functional and molecular characterization of the mammalian bed nucleus of the stria terminalis (BNST), with a focus on its medial division posteromedial compartment (BNSTmpm). The BNSTmpm is sexually dimorphic across many mammalian species, and it has been implicated in a diversity of social interactions in both sexes and physiological responses. Consistent with these observations, BNSTmpm neurons express the enzyme aromatase that converts testosterone or related androgens into estrogens; aromatase activity is essential for wildtype sexual differentiation of the brain and behavior in both sexes in rodents and many other animals. However, the function of aromatase in different brain regions in adult animals remains poorly characterized. The research goals of the diversity supplement fit within the goals of the parent project, and in particular they are focused on a subset of the specific aims. We have identified a small subset of BNSTmpm neurons that are activated upon mating in females. In aim 1 of the supplement, we will use FosTrap to label these neurons and use fiber photometry to understand the specific components of mating that activate these cells. We will next use chemogenetic actuators to test if these mating-activated BNSTmpm neurons are necessary or sufficient for female reproductive behaviors. In aim 2 of the supplement, we will specifically delete aromatase in BNSTmpm neurons to test its functional contribution to sexually dimorphic social interactions and physiology in both sexes. In summary, the studies proposed for the diversity supplement fit within the overarching goals of the parent project. Health Relatedness: Neurodegenerative and psychiatric conditions often reflect dysfunction of neural circuitry at a gross or microscopic level, and these remain poorly understood and therapeutically intractable. The BNST is a critical node linking amygdalar, hypothalamic, and cortical networks in the regulation of social interactions, response to various stressors, and reward pathways. Our proposed studies will shed light on the connectivity and functions of a subset of BNST neurons in the two sexes, thereby leading to an advance in basic scientific understanding of this region and the neural circuits within which it functions in health, and it may ultimately provide insights into future therapeutic or diagnostic applications for mental illness and common neurodegenerative conditions.

项目摘要 社会互动受到内在生理状态和未来目标的强烈影响。我们的目标是 该项目是对哺乳动物终纹床核的功能和分子特征的研究 (BNST)，重点放在其内侧部后内侧隔(BNSTmpm)。BNSTmpm是性的 在许多哺乳动物物种中都是二态的，而且它参与了多种社会相互作用 性别和生理反应。与这些观察结果一致的是，BNSTmpm神经元表达 将睾酮或相关的雄激素转化为雌激素的酶；芳香酶的活性是 对啮齿动物和许多其他动物的大脑和行为的野生型性别分化是必不可少的 动物。然而，成年动物不同脑区芳香化酶的功能仍然很差。 特色化的。多样性补充的研究目标符合母项目的目标，并符合 具体地说，他们专注于特定目标的一个子集。我们已经确定了BNSTmpm的一个小子集 雌性交配时被激活的神经元。在附录的目标1中，我们将使用FosTrap来标记 并使用纤维光度法来了解激活这些神经元的交配的特定成分 细胞。接下来，我们将使用化学致动器来测试这些交配激活的BNSTmpm神经元是否 对女性生殖行为来说是必要的或充分的。在补编的目标2中，我们将具体删除 BNSTmpm神经元中的芳香化酶，以测试其对性二态社会互动和 男女都有生理上的问题。综上所述，就多样性补充提出的研究符合 父项目的总体目标。 与健康相关：神经退行性疾病和精神疾病通常反映神经回路功能障碍 在大体或微观层面上，这些问题仍然知之甚少，在治疗上也难以解决。英国国民警卫队 是连接杏仁核、下丘脑和大脑皮层网络的关键节点，在社会互动的调节中， 对各种压力源的反应，以及奖励途径。我们提议的研究将有助于揭示 以及两性BNST神经元的子集的功能，从而导致基础科学的进步 了解这一区域以及它在其中发挥作用的神经回路，最终可能会 提供对未来精神疾病和常见疾病的治疗或诊断应用的见解 神经退行性疾病。